Jonathan L. Slaughter, MD, MPH is an Assistant Professor in the Center for Perinatal Research at Nationwide Children's Hospital and The Ohio State University. His career goal is to improve neonatal care through rigorous comparative effectiveness research (CER) that will evaluate the risks and benefits of medications that, despite limited evidence, are commonly used in the treatment of prematurity-related disorders. The proposed four-year K08 mentored career development proposal will provide Dr. Slaughter with training in CER through 1) mentorship and didactic training in longitudinal analysis of large inpatient databases 2) training in advanced statistical techniques to investigate causal inference in observational data and 3) the use of database linkages to increase the robustness of outcome estimates. Additionally, he will gain a basic knowledge of clinical trial design, an important research skill for CER investigators. The objective of Dr. Slaughter's proposed research investigation is to utilize real-world patient data from multiple sites to determine the comparative effectiveness of non-steroidal anti-inflammatory drug (NSAID) treatment for patent ductus arteriosus (PDA) versus no treatment on mortality, development of bronchopulmonary dysplasia (BPD), and duration of respiratory support. The presence of a PDA in preterm infants is associated with increased mortality and higher rates of BPD. Ductal closure by administration of NSAIDs aims to reduce these complications. However, NSAIDs are not without side effects and evidence for their benefit in improving important patient-centered outcomes is lacking. Likely due to this absence of clear evidence, there is marked between-hospital practice variation for NSAID treatment of PDA. The primary data source will be the Pediatric Health Information System (PHIS), an administrative database inclusive of most large, U.S. children's hospitals that contains daily, patient-specific data on prescribed medications and respiratory support. The specific aims of the research plan are 1) to determine factors associated with between-hospital variation in NSAID treatment for PDA, 2) determine the comparative effectiveness of various NSAID treatments versus no treatment for PDA on mortality and respiratory outcomes, and 3) to validate Aim 1 and Aim 2 results within the subset of study infants represented in both PHIS and the Children's Hospital Neonatal Database (CHND). CHND is a smaller, clinical survey database with additional and more detailed, patient-specific diagnostic and procedural data. Two internationally renowned epidemiologists, Mark Klebanoff, MD, MPH and Thomas Newman MD, MPH, and Patricia Reagan, PhD, an economist with expertise in both longitudinal data analysis and econometric causal inference methods, will serve as mentors. Other consultants will provide cardiologic expertise (Vidu Garg, MD) and assist with merger of the PHIS and CHND databases (Matt Hall, PhD). In addition to preparing Dr. Slaughter to become an independent expert in neonatal comparative effectiveness research, we expect our findings to inform patient care for preterm infants with PDA and guide the development of prospective investigations.